Disease relevance of HXT1

• The HXT1 regulatory element was then fused to the minimal cytomegalovirus promoter (HXT1-MIN) and inserted into an adenovirus for delivery to human fibroblasts, where it exhibited glucose-dependent transcriptional activation [1].
• We carried out a screen for Cryptococcus neoformans genes involved in resistance to copper ion toxicity and identified a new hexose transporter (Hxt) gene, HXT1 [2].

High impact information on HXT1

• Functional expression of the gene termed HXT1 in Saccharomyces cerevisiae and Xenopus laevis oocytes assigned a substrate specificity for D-glucose and D-fructose and indicated a proton symport mechanism [3].
• Abs against HXT1p exclusively labeled haustoria in immunofluorescence microscopy and the haustorial plasma membrane in electron microscopy [3].
• We have isolated the HXT1 gene, which encodes a low-affinity, high-capacity glucose transporter, as a multicopy suppressor of a gsf2 mutation [4].
• It was surprising that the same residues were not important for the role of Grr1 in nutrient-regulated transcription of HXT1 or AGP1 [5].
• HXT1 expression is also induced by high glucose levels through another regulatory mechanism: rgt1 mutants still require high levels of glucose for maximal induction of HXT1 expression [6].

Biological context of HXT1

• This relationship was in broad agreement with the transport kinetics of Hxt1-Hxt7 and Gal2 deduced in previous studies on single-HXT strains [7].
• The gene HXT1 (hexose transport), isolated from plasmid pSC7, was sequenced and found to encode a hydrophobic protein which is highly homologous to the large family of sugar transporter proteins from eucaryotes and procaryotes [8].
• Transcription of various known glucose transporter genes (HXT1, HXT3, and HXT4) was defective in HTR1 mutants, leading us to suggest that HTR mutations affect a negative factor of HXT gene expression [9].
• A glucose response element from the S. cerevisiae hexose transporter HXT1 gene is sensitive to glucose in human fibroblasts [1].
• In virulence tests, an hxt1 mutant strain showed 12% less phenoloxidase activity than the wild-type strain, and no difference in the ability to form melanin was identified [2].

Anatomical context of HXT1

• Efficient export of the glucose transporter Hxt1p from the endoplasmic reticulum requires Gsf2p [4].
• Thus, elements of the S.cerevisiae HXT1 gene conserve glucose regulation in human fibroblasts equivalent to the metabolism-dependent, glucose-repressing pathway in yeast [1].
• Although Hxt1p-GFP was evenly distributed through the whole cell surface, Can1p-GFP and Pma1p-GFP were confined to characteristic subregions in the plasma membrane [10].

Associations of HXT1 with chemical compounds

• The HXT1 protein is 69% identical to GAL2 and 66% identical to HXT2, and all three proteins were found to have a putative leucine zipper motif at a consensus location in membrane-spanning domain 2 [8].

Physical interactions of HXT1

• Multicopy expression of the HXT1 gene restored high-affinity glucose transport to the snf3 mutant, which is deficient in a significant proportion of high-affinity glucose transport [8].
• Comprehensive analysis of chimeras of these two proteins has previously revealed that TMs 1, 5, 7, and 8 of Hxt2 are required for high affinity glucose transport activity and that leucine 201 in TM5 is the most important in this regard of the 20 amino acid residues in these regions that differ between Hxt2 and Hxt1 [11].

Regulatory relationships of HXT1

• Active Snf1 protein kinase inhibits expression of the Saccharomyces cerevisiae HXT1 glucose transporter gene [12].
• It is likely that Rgt1 stimulates the expression of an activator of the HXT1 gene at high concentrations of glucose [13].

Other interactions of HXT1

• One suppressor encodes the previously identified glucose transporter HXT1, and another encodes a new member of this family, HXT3 [14].
• The HXT genes (HXT1 to HXT4) of the yeast Saccharomyces cerevisiae encode hexose transporters [6].
• Components of the glucose repression pathway (Hxk2p and Reg1p) are also required for generation of the high-level glucose induction signal for expression of the HXT1 gene [6].
• Transcription of HXT1-HXT7 was correlated with the extracellular glucose concentration in the cultures [7].
• The consequence of relieving feedback regulation of STD1 expression is that reestablishment of repression of HXT1 expression upon removal of glucose is delayed [15].

Analytical, diagnostic and therapeutic context of HXT1

• The V(max) of glucose transport dropped considerably and Northern blot analysis showed that induction of the HXT1, HXT2 and HXT4 genes was strongly reduced [16].

References